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Strychnine is considered a selective competitive antagonist of glycine gated Cl− channels (Saitoh et al., 1994) and studies have used strychnine at low micromolar concentrations to study the role of glycine in rabbit retina (Linn, 1998; Protti et al., 2005). However, other studies have shown that strychnine, in the concentrations commonly used, is also a potent competitive antagonist of α7 nicotinic acetylcholine receptors (nAChRs; Matsubayashi et al., 1998). We tested the effects of low micromolar concentrations of strychnine and 3-[2′-phosphonomethyl[1,1′-biphenyl]-3-yl] alanine (PMBA), a specific glycine receptor blocker (Saitoh et al., 1994; Hosie et al., 1999) on the activation of both α7 nAChRs on retinal ganglion cells and on ganglion cell responses to a light flash. Extracellular recordings were obtained from ganglion cells in an isolated retina/choroid preparation and 500 μM choline was used as an α7 agonist (Alkondon et al., 1997). We recorded from brisk sustained and brisk transient OFF cells, many of which have been previously shown to have α7 receptors (Strang et al., 2005). Further, we tested the effect of strychnine, PMBA and α-bungarotoxin on the binding of tetramethylrhodamine α-bungarotoxin in the inner plexiform layer. Our data indicates that strychnine, at doses as low as 1.0 μM, can inhibit the α7 nAChR-mediated response to choline, but PMBA at concentrations as high as 0.4 μM does not. Binding studies show strychnine and α-bungarotoxin inhibit binding of labeled α-bungarotoxin in the IPL. Thus, the effects of strychnine application may be to inhibit glycine receptors expressed by ganglion cell or to inhibit amacrine cell α7 nAChRs, both of which would result in an increase in the ganglion cell responses. Further research will be required to disentangle the effects of strychnine previously believed to be caused by a single mechanism of glycine receptor inhibition.

Acetylcholine, acting through nicotinic acetylcholine receptors,
mediates the response properties of many ganglion cells in the rabbit
retina, including those that are directionally selective (DS; Ariel
& Daw, 1982a,b). For example, Grzywacz et al. (1998) showed that cholinergic input is necessary
for DS responses to drifting gratings, a form of textured stimulus.
However, the identities and locations of the neuronal acetylcholine
receptor (nAChR) subtypes that mediate this input are not clear (Keyser et al., 2000). We investigated the role of
methyllycaconitine-sensitive, α7-like nAChRs in mediating DS
responses to textured stimuli and apparent motion. We recorded
extracellularly from On–Off DS ganglion cells in rabbit retina
using everted eyecup preparations. Our data provide evidence that
MLA-sensitive nAChRs are involved in mediating directionally selective
responses to apparent motion and to a variety of complex, textured
stimuli such as drifting square-wave gratings, transparent motion, and
second-order motion.

The responses of many ganglion cells in the rabbit retina are
mediated, at least in part, by acetylcholine (ACh) acting on
neuronal nicotinic acetylcholine receptors (nAChRs). nAChRs
are comprised of α and β subunits; three β subunits
and nine α subunits of nAChRs have been identified and these
subunits can combine to form a large number of functionally
distinct nAChR subtypes. We examined the effects of cholinergic
agents on the light-evoked responses of ganglion cells to determine
which nAChR subtypes mediate the effects of ACh. Extracellular
recordings of retinal ganglion cells were made in intact everted
eyecup preparations and nicotinic agonists and antagonists were
added to the superfusate. While several ganglion cell classes
exhibited methyllycaconitine (MLA) sensitivity, the directionally
selective (DS) ganglion cells were most sensitive; exposure
to 30 nanomolar MLA, a concentration reportedly too low to affect
αBgt-insensitive nAChRs, suppressed the stimulus-evoked
responses of DS cells without eliminating directional selectivity.
Epibatidine, which at low concentrations is an agonist selective
for αBgt-insensitive nAChRs, stimulated firing of various
cell types including DS ganglion cells at low nanomolar
concentrations. The effects of the various agents tested persisted
under cobalt-induced synaptic blockade. The low nanomolar MLA
and epibatidine sensitivity of DS cells suggests that DS ganglion
cells express both αBgt-sensitive and αBgt-insensitive
nAChRs. Other ganglion cell types appear to express only
αBgt-sensitive nAChRs but not αBgt-insensitive nAChRs.

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